STAT3 is an important member of the family of signal transducers and activators of transcription (STAT), and it is highly expressed in many malignant tissue type tumors and exerts a promoting effect on the tumorigenic progress. STAT3 is activated via phosphorylation after being stimulated by extracellular signals including non-receptor tyrosine kinases, cytokines and growth factors, and forms a phosphorylated STAT3 (P-STAT3). P-STAT3 would be rapidly transferred into cell nucleus and combined with the promoter of a target gene, activating the gene transcription, and further influencing the growth, proliferation and apoptosis of cells. The activation of STAT3 may result in abnormal proliferation and malignant transformation of cells, hence the STAT3 signal pathway is closely related to the occurrence and progression of tumors.
As currently researched, STAT3 is associated with a variety of human tumors, such as colon cancer, pancreatic cancer, lung cancer, lymphoma and so forth. Buettner R. summarized the intervening effect of STAT on tumors and the influence thereof on cell regulation, and discussed the regulation of the STAT signal transduction approach; and Junge WANG discussed a possible mechanism for the regulation of STAT3 signal transduction pathway on G1 to S phase of laryngocarcinoma cells, wherein it was discovered that the STAT3 signal transduction pathway may regulate the transition of G1 to S phase of laryngocarcinoma cells by adjusting the balance between CDK/Cyclin complex and members of cyclin-dependent kinase inhibitors (CKI). With the deep research on STAT3 signal pathway, the role of STAT3 playing in the process of occurrence and progression of tumors draws more and more attention, and a treatment method with STAT3 as the target, which inhibits the activation of STAT3, is expected to open up a novel approach to the treatment of certain malignant tumors.
The activation of STAT3 is achieved via phosphorylation, while the persistent phosphorylation of STAT3 in cells would lead to a series of biological effects, e.g. malignant proliferation and anti-apoptosis of cells. Thus, the use of drugs for inhibiting the phosphorylation of STAT3 is an important breakthrough point in the treatment of cancers.
ERK1/2 is one of the members of mitogen-activated protein kinase (MAPK) superfamily, and participates in a variety of biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and malignant transformation of cells; while p-ERK1/2 is a phosphorylated form of ERK1/2, and ERK1/2, after being phosphorylated, enters cell nucleus and acts on transcription factors such as c-myc, c-fos, c-jun, NF-κB, adjusts the transcription of the related genes, and further participates in growth, proliferation and apoptosis of cells. Thus, the activation of this signal transduction pathway is closely related to the occurrence and progression of tumors.
Therefore, the targeted regulation of the STAT3 and ERK signal pathways may be an important approach to the treatment of tumors. The nature world is a huge resource of drugs, and natural products are characterized by novel and various structures and act as an important source for current development of antineoplastic drugs and leading compounds of the drugs.
In view of this, the present invention is specially proposed.